Endothelial Lipase (EL) is a Triglyceride Lipase family on a par with Lipoprotein Lipase (LPL) and Hepatic Lipase (HL). Studies in the knockout mouse and transgenic mouse have indicated that Endothelial Lipase (EL) is associated with the metabolism of HDLc by the strong phospholipase activity, and Endothelial Lipase (EL) is accepted as a factor which regulates plasma HDLc levels (Non-Patent Document 1).
Plasma HDLc levels are accepted as an inverse correlate of coronary artery disease (CAD) risk. HDLc is supposed that an anti-arteriosclerosis action is shown through an anti-oxidization action, an antiinflammatory effect, a cholesterol reverse transmission action or the like, and low HDLc levels are accepted as one of the risk-factors of CAD.
Therefore, an EL inhibitor serves as a CAD therapeutic agent through the increase of HDLc, and increase of a HDLc and reduction of an arteriosclerosis pathological change part is reported by studies in EL knockout clinical mouse (Non-Patent Document 2).
These facts suggest the possibility of a selective inhibitor of EL as a therapeutic agent in lipid metabolism abnormality and arteriosclerosis.
Patent Document 1, 2 and 3 disclose various compounds having inhibitory activity on hepatic lipase and/or endothelial lipase, but acetic acid amide derivative such as the present compound has not been disclosed.
Patent Document 4 discloses a compound having inhibitory activity on triglyceride lipase, lipoprotein lipase, hepatic lipase, pancreatic lipase or endothelial lipase, but acetic acid amide derivative such as the present compound has not been disclosed.
Patent Document 5 to 13 disclose various compounds having inhibitory activity on EL, but acetic acid amide derivative such as the present compound has not been disclosed.
Patent Document 14 discloses a compound having inhibitory activity on MIF (Macrophage Migration Inhibitory Factor), but does not describe the inhibitory activity on EL and the increasing activity of HDLc.
Patent Document 15 discloses a derivative in which 2-position of benzothiazole or benzoxazole is substituted with acetic acid amide group as a compound useful for sleep disorders, but does not describe the inhibitory activity on EL.